Small cell neuroendocrine carcinoma of the urinary bladder

Summary Small cell carcinoma with the histological appearance of pulmonary small cell carcinoma is a rare tumour in the urinary bladder. In previous case reports the neuroendocrine nature of small cell bladder carcinoma has been accepted, but on review the evidence for true neuroendocrine differentiation appears unsatisfactory. In this study the histological, immunohistochemical and ultrastructural characteristics of three cases of small cell carcinoma of the urinary bladder are described. Ultrastructurally, the cytoplasm of all three tumours contained neurosecretory-type granules and each of the tumours demonstrated positive immunoreaction for two or more neuroendocrine markers, from a panel including neuron-specific enolase, chromogranin A, Leu-7, bombesin and synaptophysin. Although the combination of ultrastructural and immunohistochemical examination obviously offers the strongest evidence in establishing neuroendocrine differentiation, it is argued that immunohistochemistry alone may also yield important information in demonstrating a neuroendocrine nature, provided that at least neuron-specific enolase and synaptophysin are included as markers. The clinical relevance of identifying neuroendocrine differentiation in small cell bladder carcinoma is suggested by the favourable response to combination chemotherapy in two of our cases.     

Primary large cell neuroendocrine carcinoma of the urinary bladder

Primary large cell neuroendocrine carcinomas (LCNEC) of the urinary bladder are rare. Reported herein is a case of a primary, pure LCNEC occurring in a man. The patient was a 32-year-old man who presented with hematuria of 1 week's duration. On cystoscopic examination, a solitary mass measuring 3 cm in diameter was detected protruding from the anterosuperior wall of the urinary bladder. Two months after the primary transurethral resection, significant regrowth of the remnant mass was noted on CT, and the patient underwent a partial cystectomy. A diagnosis of LCNEC was made based upon histological and immunohistochemical findings. Tumor cells were positive for synaptophysin, chromogranin A, CD56, epithelial membrane antigen, and cytokeratin. Histologically, the tumor penetrated the deep muscle and perivesical fat. In spite of three cycles of chemotherapy, the patient developed multiple metastases in the lung and liver 10 months postoperatively. LCNEC of the urinary bladder are uncommon entities, which have a possible fatal outcome.     

Primary large cell neuroendocrine carcinoma of the urinary bladder

Reports of primary large cell neuroendocrine carcinomas of the urinary bladder are few; we identified only 2 cases in the literature. Both of these cases involved male patients with rapid progression of disease culminating in death with widespread metastases. We report a case of primary large cell neuroendocrine carcinoma of the bladder, with an admixed minor element of adenocarcinoma, in an 82-year-old man. This solitary lesion arose in a bladder diverticulum lateral to the left ureteric orifice. Two attempts at transurethral resection were unsuccessful at achieving local control. The patient underwent a partial cystectomy with left-sided pelvic lymphadenectomy following preoperative staging investigations that found no metastatic disease. Pathologically, the tumor invaded into the deep aspect of the muscularis propria, without extension into perivesical fat. The lateral resection margin was microscopically positive for tumor, but no malignancy was found in the pelvic lymph nodes. The adenocarcinoma comprised less than 5% of total tumor volume, and areas of transition between the neuroendocrine and adenocarcinoma components were apparent. The patient developed a local recurrence 8 months postoperatively, which was managed by a combination of transurethral resection and radiation therapy. Currently, the patient has no evidence of local or metastatic disease 2 years after initial diagnosis.     

Carcinosarcoma of the urinary bladder: A distinct variant characterized by small cell undifferentiated carcinoma with neuroendocrine features

Summary The clinicopathological features of two carcinosarcomas of the urinary bladder are reported. The tumours occurred in a 64- and a 66-year-old patient presenting with haematuria and both were polypoid. The epithelial component was consistent with small cell undifferentiated carcinoma with neuroendocrine differentiation, whereas the sarcomatous component did not display specific features. The carcinomatous component showed immunohistochemical reactivity for different epithelial markers as well as for chromogranin and neuron specific enolase. Conversely, the sarcomatous cells stained strongly for vimentin and in one case for muscle actin and smooth muscle actin. The differential diagnosis of biphasic tumours of the bladder is discussed and the literature reviewed.     

淋巴上皮瘤样癌临床病理学特征

目的探讨淋巴上皮瘤样癌(LELC)的临床病理学特点、诊断、鉴别诊断及预后。方法分析2008年1月至2018年12月台州恩泽医疗中心(集团)浙江省台州医院收集的21例LELC的临床资料、病理特点、免疫组织化学染色及原位杂交结果,并复习相关文献。结果21例LELC中,发生于涎腺8例、胃5例、肺6例、乳腺1例、宫颈1例。HE染色显微镜下形态相似,在丰富的淋巴细胞背景中见散在分布低分化或未分化的癌细胞,呈巢片状排列,免疫组织化学显示癌细胞表达广谱细胞角蛋白(CKpan)、p63、p40,间质反应性淋巴细胞表达CD8、CD20。原位杂交EB病毒编码的小RNA(EBER,16/21)阳性。结论LELC是少见的上皮性恶性肿瘤,大部分与EB病毒感染相关,具有独特的临床病理学特征,预后相对较好。     

Cytomorphology of lymphoepithelioma-like carcinoma of the urinary bladder: report of two cases

Lymphoepithelioma-like carcinoma (LELC) of the urinary bladder is a rare variant of high-grade urothelial carcinoma. Here, we report urine cytologic findings in two cases of this rare entity, the diagnosis of which was confirmed by histopathological examination of the resected tumors. The cytomorphologic features included large tumor cells with high nuclear to cytoplasmic ratios, vesicular chromatin, and prominent nucleoli, presented as single cells or intermixed with inflammatory cells. The differential diagnosis included otherwise typical high-grade urothelial carcinoma, reactive urothelial cells and rarely large cell lymphoma. The rarity of the tumor cells may impose a diagnostic challenge in urine specimen.     

Small cell neuroendocrine carcinoma of the urinary bladder: report of three cases with ultrastructural analysis

Three cases of small cell neuroendocrine carcinoma of the urinary bladder were studied by light and electron microscopic techniques. Dense-core, membrane-bound granules were identified in the cytoplasm of all 3 cases, substantiating the light microscopic impression of a morphologic similarity to other neuroendocrine carcinomas, such as small cell (oat cell) carcinoma of the lung. Two of the three cases showed clinical evidence of distant metastases, suggesting an aggressive biologic potential of this tumor similar to oat cell carcinoma of the lung. A partial remission was induced in these 2 cases using chemotherapy protocols similar to the drug regimens for small cell (oat cell) carcinomas of the lung. Recognition of this distinct entity has important clinical implications regarding therapeutic approach.     

Large cell neuroendocrine carcinoma of the thymus

 

Aim:

We highlight the occurrence of an unusual neuroendocrine tumour, a large cell neuroendocrine carcinoma, arising from the thymus.  

Case details:

A 68-year-old man with a history of cigarette smoking had a large mediastinal tumour arising from the thymus removed. Two years later the tumour recurred; it was debulked surgically but the patient died 2 months later. Histological examination of both tumour specimens revealed a tumour with an endocrine pattern, composed of large pleomorphic cells with large nuclei and prominent nucleoli. The mitotic count ranged from 19 to 26 per 10 high-power fields and large tracks of coagulative tumour necrosis were present. The tumour cells were strongly positive for neuron-specific enolase (NSE), chromogranin, CAM5.2 and AE1/3, with cytoplasmic dot-like accentuation for the latter three markers. The tumour fulfilled the criteria for a diagnosis of large cell neuroendocrine carcinoma.  

Conclusions:

Large cell neuroendocrine carcinoma should be distinguished from atypical carcinoid and small cell carcinoma. It is a distinctive neuroendocrine malignancy with a prognosis between that of atypical carcinoid and small cell carcinoma, and needs to be treated aggressively.     

Large cell neuroendocrine carcinoma of the ovary

Large cell neuroendocrine carcinoma of the ovary is a recently described tumour entity that is now included in the WHO classification of primary ovarian neoplasms. Although mostly in stage I at diagnosis, this tumour shows an aggressive clinical behaviour with subsequent metastases and mean survival is less than one year. In addition to the neuroendocrine carcinoma, most cases also have a malignant surface epithelial tumour component. I here report a 64-year-old woman who was operated on for a right-sided ovarian large cell neuroendocrine carcinoma without a surface epithelial component, which constitutes only the second reported tumour of this "pure" kind. Histological and immunohistochemical findings are described and a review of the literature is presented. The patient was treated postoperatively with chemotherapy. She developed bleomycin-induced lung fibrosis that responded well to treatment with steroids. There have been no signs of local tumour recurrence or metastases at follow-up examinations during the first 9 months after the operation.     

Cytologic features of clear cell carcinoma of the urethra and urinary bladder

Clear cell carcinoma (CCL) arising in the lower urinary tract is unusual and we report the cytohistologic findings of three cases retrieved from our files. All patients presented with bleeding, and the tumors were localized in either the urethra or bladder base. Filter and cytocentrifuge preparations of the urine were studied and all cases displayed numerous scattered aggregates or single tumor cells in an inflammatory background. The enlarged cells had abundant clear, wispy cytoplasm with discrete vacuolation. Hobnail and signet ring cells were apparent. The nuclei had granular to vesicular chromatin with prominent often multiple nucleoli. The tumors were histologically distinctive and typically had a tubulocystic configuration with varying proportions of papillary and diffuse patterns. One patient has died of metastatic cancer and two are presently free of tumor. The cytohistologic features of this cancer are characteristic and from our review we conclude that this lesion can be diagnosed by cytologic means. Diagn Cytopathol 1996;14:150–154. © 1996 Wiley-Liss, Inc.     

喉大细胞神经内分泌癌

目的：探讨喉大细胞神经内分泌癌的临床及病理特征。方法：复习2例患者的临床病史，肿瘤组织的病理形态和免疫表型及相关文献。结果：2例患者均为男性，以声音嘶哑、喉部不适为主要表现；病变均位于声门上，以具有丰富嗜酸性胞质，巢状排列为肿瘤细胞的形态特征，免疫组化表达神经内分泌肿瘤标志物。2例均因短期内发生肿瘤广泛转移而死亡，结论：喉大细胞神经内分泌癌属于高度恶性的肿瘤。形态上需与低分化鳞癌，甲状腺样癌，肺神经内分泌癌，副神经节瘤和无色素性黑色素瘤等相鉴别。     

Small cell carcinoma of the urinary bladder

Primary small cell carcinoma of the urinary bladder is very rare; only several studies have been reported in the English literature. A 62-year-old woman was admitted to our hospital because of hematuria and dysuria. Bladder endoscopy revealed a large polypoid tumor at the bladder base. Transurethral bladder tumorectomy (TUR-BT) was performed. Many TUR-BT specimens were obtained. Histologically, the bladder tumor was pure small cell carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK8, CK18, neurone-specific enolase, chromogranin, NCAM (CD56), synaptophysin, Ki-67 (labeling=100%), p53, KIT (CD117), and platelet-derived growth factor receptor-α (PDGFRA). The tumor cells were negative for CK5/6, CK 34BE12, CK7, CK14, CK19, CK20, p63, CD45, and TTF-1. A molecular genetic analysis using PCR-direct sequencing showed no mutations of KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. No metastases were found by various imaging techniques. The patient is now treated by cisplatin-based chemotherapy.     

膀胱小细胞神经内分泌复合癌1例报道及文献复习

目的：研究膀胱小细胞神经内分泌复合癌（ＳＣＮＥＣＣ）的临床病理特征及生物学行为。方法：采用光镜、电和免疫细胞对１例膀胱ＳＣＮＥＣＣ进行观察及行随访。结果本例肿瘤组织由小细胞神经内分泌癌，移行细胞癌及腺中闾民分构成。电镜下在小细胞癌人可找见神经内分泌颗粒，免疫组化ＮＳＥ阳性。术后３个月发生肝与肩胛骨转移，１３个月死于肝功能衰竭。结论：ＳＣＮＥＣＣ是一罕见高度恶性肿瘤，有独特的病理形态，早期即可发生侵     

Large cell neuroendocrine carcinoma of the ampulla of vater

We report a large cell neuroendocrine carcinoma arising in the ampulla of Vater. The patient, a 74-year-old woman, presented with a 3-cm ulcerated mass located in the ampullary region. She died of disease 8 months after surgery. Microscopically, the tumor was extensively necrotic. It was composed of islands and trabeculae irregularly infiltrating the muscular wall of the duodenum. Neoplastic cells were large and had a high mitotic index. Immunohistochemically, they expressed cytokeratin, chromogranin, synaptophysin, and neuron-specific enolase. Large cell neuroendocrine carcinoma is very rare in the ampulla of Vater, and it shares with its more common pulmonary counterpart the same morphology and probably the same poor prognosis.     

Transitional cell carcinoma of the urinary bladder with pseudosarcomatous stroma

An 84-year-old man who complained of hematuria had transurethral resection of a large polypoid tumor in the urinary bladder. Pathologic examination showed an invasive, moderately differentiated transitional cell carcinoma with numerous atypical mesenchymal cells in its stroma. The latter cells failed to stain immunohistochemically for epithelial markers and were interpreted as reactive or pseudosarcomatous in nature. Transitional cell carcinomas with pseudosarcomatous stroma should be distinguished from bladder tumors with a neoplastic spindle cell component such as sarcomatoid carcinomas and carcinosarcomas.     

Primary signet-ring cell carcinoma of the urinary bladder

Signet-ring cell carcinoma of the urinary bladder is a rare tumour, accounting for approximately 0.24% of all bladder malignancies. In this study, the clinicopathological findings in 13 cases are described. This malignancy is far more common in men than in women (ratio 11:2). The distribution by age and clinical symptoms can not distinguish it from transitional cell carcinoma. The tumour behaves like other high grade malignancies, presenting frequently at an advanced stage, and having an unfavourable clinical outcome. No special therapy seems superior to another.     

Glandular squamous cell carcinoma of the urinary bladder

The paper gives a clinical observation of a 52 year-old male with a rare histological urinary bladder tumor primary grandular-squamous-cell carcinoma (pT3N IM0). The tumor is represented by two components large acinic-cell adenocarcinoma and squamous-cell carcinoma with keratinization, which smoothly pass one into another; the tumor has grown through all layers of the urinary bladder wall but it has failed to grow into the peritoneum. A microscopic study has indicated that the urachus is intact. Metastases were found in 3 of 8 lymph nodes: one showed high-grade adenocarcinoma and two others displayed average-grade squamous-cell carcinoma.